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Abstract
Simple SummaryAnaplastic large cell lymphomas associated with ALK translocation have a good outcome after CHOP treatment; however, the 2-year relapse rate remains at 30%. Microarray gene-expression profiling, high throughput RT-qPCR, and RNA sequencing of 48 ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) samples obtained at diagnosis enable the identification of genes associated with clinical outcome. More particularly, our molecular signatures indicate that the FN1 gene, a matrix key regulator, might also be involved in the prognosis and the therapeutic response in anaplastic lymphomas.Anaplastic large cell lymphomas associated with ALK translocation have a good outcome after CHOP treatment; however, the 2-year relapse rate remains at 30%. Microarray gene-expression profiling of 48 samples obtained at diagnosis was used to identify 47 genes that were differentially expressed between patients with early relapse/progression and no relapse. In the relapsing group, the most significant overrepresented genes were related to the regulation of the immune response and T-cell activation while those in the non-relapsing group were involved in the extracellular matrix. Fluidigm technology gave concordant results for 29 genes, of which FN1, FAM179A, and SLC40A1 had the strongest predictive power after logistic regression and two classification algorithms. In parallel with 39 samples, we used a Kallisto/Sleuth pipeline to analyze RNA sequencing data and identified 20 genes common to the 28 genes validated by Fluidigm technology—notably, the FAM179A and FN1 genes. Interestingly, FN1 also belongs to the gene signature predicting longer survival in diffuse large B-cell lymphomas treated with CHOP. Thus, our molecular signatures indicate that the FN1 gene, a matrix key regulator, might also be involved in the prognosis and the therapeutic response in anaplastic lymphomas.
Highlights
Anaplastic large cell lymphoma (ALCL) is a rare type of T-cell lymphomas, accounting for approximately 3% of adult non-Hodgkin lymphomas and 10 to 20% of childhood lymphomas [1]
Anaplastic Lymphoma Kinase (ALK)+ ALCL tumors have a better outcome than other aggressive non-Hodgkin lymphomas, with a 5-year overall survival (OS) rate of 70% for adults and >90% for children [3,4,5,6,7,8,9,10]; the 2-year relapse rate remains at 30% [3,4,5,6,7,8,10,11]
Several prognostic factors have been recently described for paediatric ALK+ ALCLs, including the detection of minimal disseminated disease (MDD) [12], in bone marrow or blood combined with antibody titers against ALK [13,14,15,16]
Summary
Anaplastic large cell lymphoma (ALCL) is a rare type of T-cell lymphomas, accounting for approximately 3% of adult non-Hodgkin lymphomas and 10 to 20% of childhood lymphomas [1]. ALK+ ALCL tumors have a better outcome than other aggressive non-Hodgkin lymphomas, with a 5-year overall survival (OS) rate of 70% for adults and >90% for children [3,4,5,6,7,8,9,10]; the 2-year relapse rate remains at 30% [3,4,5,6,7,8,10,11]. We profiled gene expression in pre-treatment biopsies from non-relapsing and relapsing patients with ALK+ ALCL to provide an additional indicator that could help to identify patients with a high risk of relapse and those of low risk who could benefit from a therapy reduction. Fluidgim technology and the Kallisto/Sleuth pipeline helped us to cross-validate candidate genes
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